Description: (Applicant's Description) The general goal of this program is to investigate the molecular mechanisms by which betaIFN modulates the repair capacity and increases the radiation sensitivity of human lung and brain tumor cells. Recent studies in their laboratory and others have shown that betaIFN increases the duration of radiation-induced G2/M delay. This delay is accompanied by a temporary loss of DNA binding activity of Ku 70/80. Since Ku 70/80 has been suggested to be involved in the repair of DNA strand breaks, the possible roles of Ku 70/80 and DNA-dependent protein kinase (DNA-PK) in the betaIFN induced radiation sensitivity will be examined. In addition, the roles of p34 kinase, and cyclin B in the G2/M delay induced by interferon and radiation will be determined. The central hypothesis to be tested in this program is that betaIFN either directly (DNA-PK/Ku 70/80 activity) or indirectly (cell cycle regulation) modulates the repair capacity of irradiated human lung and brain tumor cells.